During the past several years, we have been studying the regulation of protein synthesis in normal, toxically injured, and diseased liver in model systems derived from rats. Previously, we developed molecular hybridization technology to study albumin mRNA biogenesis and function. We measured subcellular distribution of albumin mRNA in the cytoplasm of normal liver and found that 97-98% of albumin mRNA sequences are located in membrane-bound polyribosomes. When rats were fasted for 24-30 hours, the bulk of albumin mRNA shifted from membrane-bound polyribosomes to mRNPs free in the cytosol, accompanied by a marked depression in albumin synthesis. In chronic renal failure in rats, we also find a marked decrease in albumin synthesis but albumin mRNA is increased rather than decreased in membrane-bound polysomes. This is associated with a balanced increase in total RNA. Using recombinant DNA techniques, we have cloned and purified albumin cDNA and fragments of albumin cDNA from various regions of the genome. We are developing techniques to use clone purified albumin cDNA as a hybridization probe to quantitate albumin mRNA. With this probe and a rat hepatoma cell line in tissue culture, we will measure transcription, processing and cytoplasmic turnover of albumin mRNA in normal and altered pathophysiologic states of these cells. We will also measure steady state levels of nuclear albumin mRNA precurser and their changes in liver under various pathologic conditions in conjunction with studies of cytoplasmic albumin mRNA function. These conditions include chronic renal failure, acute and chronic alcohol administration, protein-calorie deprivation and CC14 induced cirrhosis. These studies will hopefully advance our understanding of the molecular basis for control of albumin gene expression in normal and abnormal rat liver.